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A University of Maryland (UMD) startup has developed molecular containers that can potentially reduce the post-surgical side effects of neuromuscular blocking agents (NMBAs) administered during surgery by anesthesiologists.

A new class of molecular containers known as calabadions has been developed by UMD Professor Lyle Isaacs in the Department of Chemistry and Biochemistry. Professor Isaacs launched Calabash Bioscience, a startup that grew out of the College Park campus less than a year ago, based around his work related to calabadions. Isaacs co-founded the company along with Dr. Matthias Eikermann, Associate Professor of Anesthesia at Harvard Medical School and Director of Research of the Critical Care Division at Massachusetts General Hospital.

Calabash Bioscience’s molecular container known as Calabadion 2 binds tightly to a drug known as rocuronium that is used by anesthesiologists during surgery to prevent muscle movement in patients undergoing surgery. In the Isaacs laboratory, Calabadion 2 is affectionately referred to as ‘Motor 2’ after his former graduate student Da Ma who first synthesized it.

Other containers developed by the startup are capable of binding to antibiotics and anti-cancer drugs, among others.

Rocuronium, the neuromuscular blocking agent that Calabadion 2 is designed to counteract, has residual side effects including poor muscular function and breathing problems.

According to Isaacs, the side effects of these agents could increase mortality and hospitalization costs.

The molecular container compound developed by Calabash Bioscience can bind with rocuronium and deactivate it, thereby enabling patients to regain muscle function faster after the surgery.

“Just like in everyday life, you have containers to store something, and molecules need containers for similar reasons,” Isaacs said. “This makes our product attractive for real world applications.”

Isaacs had been looking at these molecular containers for basic scientific study and worked with anesthesiologists several years ago to prove their function of reversing neuromuscular blocking in rats.

Initial funding financed feasibility testing, after which interest from investors prompted the researchers to move towards commercialization and the formation of Calabash Bioscience.

“The earliest step in creating Calabash was the development of a proposal to TEDCO’s Maryland Innovation Initiative (MII) program, which allowed us to perform key tests to reduce the risk of our project to potential investors,” Isaacs said.

He believes that the product has great potential to impact important drug application areas and has a good chance of being approved by the U.S. Food and Drug Administration (FDA). Bridion was a product by Merck that performed similar functions, but was rejected three times by the FDA.

“There’s clearly market demand. Merck is making money off of Bridion in Europe and tried hard to get it approved in the United States, unsuccessfully. This is a well-known problem in anesthesiology in the U.S. market. We believe our product can address this problem and has great potential,” Isaacs said.

The next steps in the development of Calabash Bioscience’s products are being conducted with the help of contract research organizations.

Isaacs said that the Office of Technology Commercialization (OTC) has been very supportive. “The OTC has been great in support of patenting and also in terms of professional development and valued advice,” he said.

The product has been tested in vivo in rats and human testing is anticipated down the road, Isaacs said, talking about future plans.

“Depending on our initial results, we will see if the FDA will allow us to get on to an Investigational New Drug (IND) Application,” he said.